ACTION: Autologous CD30.CAR-T in Combination With Nivolumab in cHL Patients After Failure of Frontline Therapy

Sponsor

Tessa Therapeutics (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05352828

Collaborator

Bristol-Myers Squibb (Industry)

Enrollment

Locations

Arm

184.7

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 1b, multicenter, open-label, single arm study to evaluate the safety and efficacy of the combination therapy, CD30.CAR-T and the programmed cell death protein-1 (PD-1) checkpoint inhibitor, nivolumab, in patients aged 12 years of age and above with relapsed or refractory classical Hodgkin lymphoma (cHL) following failure of standard frontline therapy.

Condition or Disease	Intervention/Treatment	Phase
Classical Hodgkin Lymphoma Hodgkin Disease Refractory Hodgkin Disease Recurrent	Drug: Nivolumab Drug: Autologous CD30.CAR-T Drug: Fludarabine Drug: Bendamustine	Phase 1

Detailed Description

Study Design

Study Type:

Interventional

Anticipated Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Upon successful leukapheresis to produce CD30.CAR-T cells, patients will enter the treatment phase of the study. Treatments will include 4 cycles of nivolumab and CD30.CAR-T infusion (preceded by lymphodepletion chemotherapy). Patients will then enter the post-treatment follow-up phase of the study, whereby patients will undergo either autologous stem cell transplant or continue to receive up to 6 additional treatment cycles of nivolumab. Patients will be followed for response assessments and safety monitoring until end of study (EOS); approximately 3 years after leukapheresis. Long-term follow-up will continue with additional safety monitoring and survival for up to 15 years after Leukapheresis.Upon successful leukapheresis to produce CD30.CAR-T cells, patients will enter the treatment phase of the study. Treatments will include 4 cycles of nivolumab and CD30.CAR-T infusion (preceded by lymphodepletion chemotherapy). Patients will then enter the post-treatment follow-up phase of the study, whereby patients will undergo either autologous stem cell transplant or continue to receive up to 6 additional treatment cycles of nivolumab. Patients will be followed for response assessments and safety monitoring until end of study (EOS); approximately 3 years after leukapheresis. Long-term follow-up will continue with additional safety monitoring and survival for up to 15 years after Leukapheresis.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase 1b Study Evaluating the Safety and Efficacy of Autologous CD30.CAR-T in Combination With PD-1 Checkpoint Inhibitor (Nivolumab) in Relapsed or Refractory Classical Hodgkin Lymphoma Patients After Failure of Frontline Therapy (ACTION)

Actual Study Start Date :

Jul 25, 2022

Anticipated Primary Completion Date :

Dec 15, 2025

Anticipated Study Completion Date :

Dec 15, 2037

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nivolumab and CD30.CAR-T Study treatment will include 4 cycles of nivolumab and a single CD30.CAR-T infusion (preceded by lymphodepletion chemotherapy of Fludarabine and Bendamustine).	Drug: Nivolumab Dose: 480 mg or 6 mg/kg Q4W Other Names: Opdivo Drug: Autologous CD30.CAR-T Dose: 2 x 10e8 cells/m2 Other Names: CD30-directed CAR-T cells Drug: Fludarabine Dose: 30 mg/m2/day x 3 days Other Names: Fludara Drug: Bendamustine Dose: 70 mg/m2/day x 3 days Other Names: Bendeka Treanda

Arm

Intervention/Treatment

Experimental: Nivolumab and CD30.CAR-T

Study treatment will include 4 cycles of nivolumab and a single CD30.CAR-T infusion (preceded by lymphodepletion chemotherapy of Fludarabine and Bendamustine).

Drug: Nivolumab

Dose: 480 mg or 6 mg/kg Q4W

Other Names:

Opdivo

Drug: Autologous CD30.CAR-T

Dose: 2 x 10e8 cells/m2

Other Names:

CD30-directed CAR-T cells

Drug: Fludarabine

Dose: 30 mg/m2/day x 3 days

Other Names:

Fludara

Drug: Bendamustine

Dose: 70 mg/m2/day x 3 days

Other Names:

Bendeka

Treanda

Outcome Measures

Primary Outcome Measures

Safety of autologous CD30.CAR-T in combination with nivolumab [From first dose of nivolumab (Cycle 1) to end of nivolumab Cycle 4 (each cycle is 28 days)]
DLT

Secondary Outcome Measures

Anti-tumor activity using CR rate of autologous CD30.CAR-T in combination with nivolumab [Up to end of 10 weeks post-CD30.CAR-T treatment]
CR rate
Overall response rate [Through study completion, an average of 3 years from Leukapheresis]
ORR
Duration of response [Through study completion, an average of 3 years from Leukapheresis]
DOR
Progression-free survival [Through study completion, an average of 3 years from Leukapheresis]
PFS

Other Outcome Measures

Overall survival [Through study completion, an average of 3 years from Leukapheresis]
OS
Pharmacokinetics - Maximum concentration (Cmax) [Through study completion, an average of 3 years from Leukapheresis]
Maximum concentration of CD30.CAR-T
Pharmacokinetics - Time of maximum concentration (Tmax) [Through study completion, an average of 3 years from Leukapheresis]
Time to peak concentration of CD30.CAR-T in the blood
Pharmacokinetics - Area under the curve [Through study completion, an average of 3 years from Leukapheresis]
Area under the curve of CD30.CAR-T in the blood

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Signed ICF
Male or female patients who are 12 years of age and above
Relapsed or refractory CD30+ cHL following failure of a standard frontline chemotherapy
At least 1 lesion, which must be fluordeoxyglucose positron emission tomography (FDG-PET) avid and measurable by PET-CT scan
Adequate laboratory parameters including hematologic, renal, hepatic, and coagulation function
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, or equivalent either Karnofsky performance status (for patients ≥ 16 years of age) or Lansky performance status (for patients < 16 years of age)
Anticipated life expectancy > 12 weeks
No active infections including COVID 19 at Screening

Exclusion Criteria:

Evidence of lymphomatous involvement of the central nervous system (CNS)
Presence of clinically relevant or active seizure disorder, stroke, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with central nervous system (CNS) involvement
Symptomatic cardiovascular disease: Class III or IV according to the New York Heart Association (NYHA) Functional Classification
Active uncontrolled bleeding or a known bleeding diathesis
Inadequate pulmonary function defined as oxygen saturation by pulse oximetry < 90% on room air
Echocardiogram (ECHO) or Multi-gated Acquisition (MUGA) scan with left ventricular ejection fraction (LVEF) < 45%
Prior receipt of salvage therapy, for relapsed or refractory cHL, including allogeneic or ASCT
Prior receipt of investigational CD30.CAR-T cells
Receiving any investigational agents or any tumor vaccines
Receiving any live/attenuated vaccines
Ongoing treatment with immunosuppressive drugs or chronic systemic corticosteroids
Unresolved > Grade 1 non-hematologic toxicity associated with any prior treatments
Previous history of known or suspected autoimmune disease within the past 5 years
Active interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
Evidence of human immunodeficiency virus (HIV) infection
Evidence of active viral infection with hepatitis B virus (HBV)
Evidence of active viral infection with hepatitis C virus (HCV)
Active second malignancy or history of another malignancy within the last 3 years
History of hypersensitivity reactions to murine protein-containing products or other product excipients
Any allergic or adverse reaction to nivolumab, fludarabine, or bendamustine that precludes treatment with these agents
History of a significant irAE from prior immune checkpoint inhibitor therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope National Medical Center	Duarte	California	United States	91010
2	University of Miami	Miami	Florida	United States	33136
3	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599
4	Baylor College of Medicine	Houston	Texas	United States	77030
5	MD Anderson Cancer Center	Houston	Texas	United States	77030